Organic Chemistry, Martin-Luther University Halle-Wittenberg, Kurt-Mothes, Str. 2, D-06120 Halle (Saale), Germany.
Natural & Medical Sciences Research Center, University of Nizwa, Nizwa 616, Oman.
Molecules. 2024 Jun 25;29(13):3015. doi: 10.3390/molecules29133015.
A small library of 79 substituted phenylsulfonamidoalkyl sulfamates, -, was synthesized starting from arylsulfonyl chlorides and amino alcohols with different numbers of methylene groups between the hydroxyl and amino moieties yielding intermediates -, followed by the reaction of the latter with sulfamoyl chloride. All compounds were screened for their inhibitory activity on bovine carbonic anhydrase II. Compounds - showed no inhibition of the enzyme, in contrast to sulfamates -. Thus, the inhibitory potential of compounds - towards this enzyme depends on the substituent and the substitution pattern of the phenyl group as well as the length of the spacer. Bulkier substituents in the position proved to be better for inhibiting CAII than compounds with the same substituent in the or position. For many substitution patterns, compounds with shorter spacer lengths were superior to those with long chain spacers. Compounds with shorter spacer lengths performed better than those with longer chain spacers for a variety of substitution patterns. The most active compound held inhibition constant as low as K = 0.67 μM (for ) and a -butyl substituent in position and acted as a competitive inhibitor of the enzyme.
从芳基磺酰氯和氨基醇出发，合成了一个包含 79 个取代的苯磺酰胺基烷基磺酸盐的小文库，-，这些氨基醇在羟基和氨基部分之间具有不同数目的亚甲基。得到中间体-，然后后者与磺酰氯反应。所有化合物都进行了对牛碳酸酐酶 II 的抑制活性筛选。与磺酰胺基-相比，化合物-对该酶没有抑制作用。因此，化合物-对该酶的抑制潜力取决于苯基取代基和取代模式以及间隔基的长度。在 位置上带有较大取代基的化合物比在 或 位置上具有相同取代基的化合物更能抑制 CAII。对于许多取代模式，短间隔基的化合物优于长链间隔基的化合物。对于各种取代模式，短间隔基的化合物比长链间隔基的化合物表现出更好的性能。最活性化合物的抑制常数低至 K = 0.67 μM（对于），并且在 位置上具有 -丁基取代基，并且作为该酶的竞争性抑制剂。
